Skeletal muscle represents the largest organ mass in the body. It also represents the largest reserve of body protein. It is well established that advancing age is associated with a decline in skeletal muscle mass. However, it is not clear whether this decreased muscle mass is a result of aging per se, a chronic reduced level of physical activity which accompanies senescence, increased myofibrillar protein turnover, nutritional inadequacies, or the onset of disease processes. Our laboratory has demonstrated that eccentric exercise (a component of all exercise) causes muscle damage which results in a prolonged increase in the rate of protein degradation. Our data implicate the exercise-induced increase in circulating interleukin-1 and prolonged increase in skeletal muscle interleukin-1B as a mediator of these changes. In addition, we have demonstrated that older subjects experience more muscle damage and increased rates of myofibrillar protein degradation when compared to young subjects. However, the mechanisms for changes in muscle protein turnover following exercise are not well understood. The proposed studies will for the first time examine the effects of eccentric exercise on ubiquitin- mediated muscle protein degradation and the fractional rate of muscle protein synthesis in the elderly. We will use eccentric exercise to stimulate changes in muscle metabolism in older men and women. Specific mediators of proteolysis will be quantified with immunohistochemical techniques.